I have had the opportunity for the last 15 years to develop a clinical research career in nutritional and more recently, metabolic issues in patients infected with HIV. The purpose of this application for a mid career award in patient oriented research is to facilitate my ability to perform clinical research and to mentor trainees in clinical research in HIV related research questions. As HIV has become more of a chronic, manageable infection in the developed world, the ability to define, understand and manage the nutritional and metabolic issues in HIV-infected patients has become critical to permit optimization of duration and quality of life. Although the use of Highly Active Antiretroviral Therapy (HAART) has dramatically reduced the frequency of opportunistic infections and death in HIV, long-term complications of HIV and HAART remain common. While the severe wasting that was one of the most frequent AIDS defining illnesses in HIV infected patients in the earlier days of the epidemic has declined in frequency, the occurrence of significant weight loss has continued to be common in these patients and the etiologies and long term medical impact of this weight loss remains to be determined. As the institution of HAART therapy has dramatically reduced the number of HIV-associated deaths and the numbers of opportunistic illnesses, the increased life span (and aging) of patients infected with HIV and treated with HAART has revealed additional nutritional and metabolic issues in these patients. There is increasing concern that one of the long-term side effects of HAART (or potentially the increased survival with HIV) may include an increased risk for cardiovascular disease. The potential for increased cardiovascular risk in HIV infection requires additional investigation and if real, will require investigations to define the etiology and predictors of this risk as well as the development of means to intervene and reduce this risk. Underlying all of the metabolic issues in HIV is a more basic question, that is, the role of the specific characteristics of the virus and the role of chronic infection with HIV, and the resulting chronic inflammatory changes on metabolic and physiological function in infected patients. I hope to be able to work toward some elucidation of these issues with the support of this award. In addition, this award will support my ability to mentor trainees in these important clinical research questions. [unreadable] [unreadable]